Several studies have shown that probiotics and synbiotics ameliorate dyslipidemia. However, the molecular mechanisms mediating their effects remain to be determined. Therefore, we aimed to compare the effects of a probiotic, a prebiotic, and a synbiotic in dyslipidemic Sprague-Dawley rats, and explore the mechanisms involved using a proteomic approach. The rats were allocated to five groups: a control group that was fed normal chow, and four high-fat diet-fed groups, three of which were administered a probiotic (Lactobacillus acidophilus), a prebiotic (inulin), or a combination of the two (a synbiotic) for 30 days. We showed that the administration of inulin, and especially L. acidophilus, improved the lipid profile and reduced the serum concentrations of inflammatory markers in high-fat diet-fed rats. Proteomic analysis showed changes in lipid elongation, glycerolipid metabolism, activation of antioxidants, and a reduction in the activation of the mitogen-activated protein kinase signaling pathway in the livers of rats administered L. acidophilus, which likely mediate its beneficial effects on inflammation and dyslipidemia by reduced the levels of 18.56% CRP, 35.71% TNF-α 25.6% LDL-C and 28.57% LDL-C/HDL-C ratio when compared to HF group. L. acidophilus and inulin may represent effective natural means of maintaining inflammation and dyslipidemia.